The present invention relates to configurable and/or reconfigurable microreactor networks, i.e. microfluidic systems comprising microreactors and interconnecting microchannels whose interconnections are designed for single configuration, multiple configuration or dynamic configuration, i.e. they are switchable or reconfigurable.
Such microfluidic systems allow custom-tailored microreactor networks or evolvable microreactor networks to be set up. Any number of said microreactors can be connected in series or in a modular construction above each other such that completely configurable switchable networks of microfluidic systems are produced.
It is an object of the present invention to provide microfluidic systems, i.e. configurable microreactor networks which have an extremely high integration density, without the requirement of flexibility and variability of the interconnection of microchannels being deleteriously affected.
According to the present invention this object is solved with a configurable microreactor network according to claim 1. The microreactor network of the invention is preferably provided with
a substrate,
a plurality of microreactors arranged in the substrate for chemical and/or biological and/or biochemical and/or other type of processing and/or treatment of chemical and/or biological and/or biochemical substances,
first channels arranged in the substrate and divided into first groups, wherein each first channel group comprises at least one first channel, and wherein the microreactors are arranged between adjacent first channel groups,
second channels arranged in the substrate and extending above or below the first channels, said second channels being divided into second groups, wherein each second channel group comprises at least one second channel, and wherein the microreactors are arranged between adjacent second channel groups,
first branch channels starting from the microreactors, said first branch channels being arranged in the substrate and extending at least above or below the second channels of the respective adjacent second channel groups,
second branch channels starting from the microreactors, said second branch channels being arranged in the substrate and extending at least above or below the first channels of the respective first channel groups adjacent the microreactors, and
a plurality of connecting channel arrangements disposed at at least some of the point of overpassings of the first and second channels, of the first branch channels and the second channels, and of the second branch channels and the first channels, wherein each connecting channel arrangement comprises:
connecting channels between the at least two channel sections of the first and second channels and/or branch channels leading to a point of overpassing,
wherein the connecting channels extend from each channel section of a point of overpassing to the respective other channel sections of said point of overpassing, and
wherein in the connecting channels blocking elements are arranged for optionally blocking the fluid connection provided by a connecting channel for the purpose of blocking/releasing the fluid connection between the at least two channel sections of a point of overpassing.
The main aspect of the solution according to the present invention is the flexibility of groups of first and second channels and/or first and second branch channels overpassing each other in different planes, wherein the first and second channels extend at an angle, in particular perpendicular to each other between the microreactors preferably arranged in an orthogonal network, and the first and second branch channels starting from the individual microreactors extend to the first and second channels. The channel sections of the at least two channels forming the point of overpassing extend to a point of over(under-)passing and can be selectively and individually connected via a network of connecting channels. When producing these connecting channel networks (referred to above as connecting channel arrangement) it must be ensured that a channel section is selectively connectable with another channel section leading to an overpassing region and, selectively, certain channel section are not interconnected. This is effected by selective insertion of blocking elements or insertion of materials or structures into the connecting channels and/or the channel sections leading to an overpassing region or arranged therein, which allows a connecting channel or channel section to be blocked or released by selectively activating said materials or structures after production of the connecting channel networks. This offers an extremely high degree of both irreversible and reversible configurability. The term xe2x80x9coverpassing pointxe2x80x9d or xe2x80x9ccrossing pointxe2x80x9d is meant to denote a region in which channel sections overpass each other or terminate close to each other. These channel sections which possibly do not overpass each other are connected via connection channels which themselves can overpass or cross each other and thus represent an overpass or crossing of the channel sections.
The configurable microreactor networks according to the present invention are produced according to a new method. This new technology allows a so-called xe2x80x9cmasterchipxe2x80x9d to be produced first which is provided, by subsequent progamming, with the interconnection of its microchannels as required for the respective application. xe2x80x9cProgrammingxe2x80x9d means both insertion of invariable blocking elements into the connecting channels between adjacent branching points of the connecting channels (this is, so to say, one of the last steps during chip production), and programming of the chip by corresponding treatment (chemical, optical, electrical, precise-mechanical, thermal, biological etc.) to subsequently activate or deactivate materials or structures inserted into the connecting channel arrangements.
The microreactor network according to the present invention is preferably employed in the field of microreactor technology, biology, combinatorial chemistry, clinical diagnostics, active substance screening in the pharmaceutical research or DNA-computing. New methods for producing pharmaceuticals and chemicals can be tested and optimized considerably faster and thus more effectively without laborious development and testing of new microsystems.
One main aspect of the microreactor network according to the present invention are connecting elements (referred to above as blocking elements which can be changed over between a blocking and a release position) which are in particular of bistable and whose state can be switched once (for configuration of the microreactor network) or repeatedly (for configuration or reconfiguration of the microreactor network) to regulate the connecting channel arrangements. The blocking element variant of once-only switchable configuration is an integrable element which has a higher density than blocking elements of the multiply switchable configuration since, in the first case, the infrastructure for the reprogramming of the blocking elements is not required,
Besides the possibility to select the microreactors of the array by providing the connecting channel arrangements with blocking elements which cannot be changed over by the user, the following three embodiments and development stages are further conceivable.
1. Irreversible user-programmable array of bistable blocking elements
Specified design measures with previously specified optimized design steps allow standardized microfluidic systems to be prefabricated in large quantities (inexpensively) up to this process stage. The production process starts with CAD mask designing of channel structures and process elements. Thereafter, the photolithographic thin-film process stages required for microstructuring the substrate are performed. Only during the last production stages the system is configured once for the special application by releasing or blocking individual microchannels. This can be realized at a considerably smaller expenditure and complexity with regard to devices employed and/or clean room requirements at smaller resolution or by faster progamming. Thus a very high integration density (integration of a plurality of different microreactors) is attained, which is not least due to the fact that appropriately bistable elements are employed as blocking elements which automatically, i.e. without permanent application of control signals, maintain their respective position (blocking or release position).
2. Independently irreversible and jointly reprogrammable array of bistable blocking elements
Prior to commencement of the special application, the connecting structure is configured by releasing or blocking individual microchannels. At the end of the application, this configuration can be cancelled by restoring the complete simple initial state, and the microfluidic system can be employed for another application.
Example: Photo-induced and/or photo-assisted local polymerization. At the end of the application destruction of all polymeric plugs by means of a solvent.
3. Independently reversibly reprogrammable array of bistable blocking elements
At the beginning of and during an application the connecting structure is configured or reconfigured by releasing or blocking individual microchannels by means of dynamically switchable bistable (switching) elements. Since the elements are bistable, they may be successively configured without the control signals or control lines being permanently maintained. This allows, besides inexpensive production, the microfluidic systems to be controlled, regulated, optimized and evolved during the application process in order to use them later for another application.
The microreactor network according to the present invention may be produced as follows.
The reactor cell elements, the main inlet channels, the horizontal supply channels and the switching elements are inserted into the substrate (e.g wafer) by means of the microstructuring method. The substrate is structured on both sides.
For this purpose wet-chemical or physical etching techniques may be applied for structuring silicon and photostructurable glass; galvanic, erosive and micromechanical methods (sawing, cutting, milling, turning) may be applied for machining metals; and laser structuring methods or molding techniques may be applied for processing polymeric materials and functional ceramics.
The reactor cell elements (process elements) may both act as an independent process unit and be designed as a self-programmable unit in that mixing, transporting, reacting, detecting and separating components are integrated in a process element and switched on and off according to requirement.
The substrate containing the so produced structures is sealingly closed by a cover plate made of glass or a transparent polymeric material (bonding, glueing, laminating, ultrasonic and laser welding etc.).
Integration of reconfigurable switching elements: Simple blocking of the channels, e.g. optically controlled by photopolymerizable monomeric fluids, two-component resins in separated chambers, bistable switch, hydrogels, nozzle switching system, which are all electronically, electromagnetically, biologically, chemically, thermally, physically etc. switchable.
The configurable microreactor network of the invention comprises a substrate in which a plurality of over(under-)passing channels are arranged. Said channels are optionally interconnectable via connecting channel arrangements. Between said channels, microreactors are arranged which are connected with the channels. Here, too, channel-connecting arrangements are employed. Said channel-connecting arrangements comprise a plurality of connecting channels in which blocking elements can be positioned or inserted in any other way or activated. The arrangement and/or state of the blocking elements allows the highest possible integration density to be reached respectively for each of a series of specified degrees of (re-)configuration flexibility (the necessity of which depends on the application type).